The present invention relates to a method for the early diagnosis of carcinomas as well as their preliminary stages, particularly carcinomas of the upper respiratory tract or the anogenital tract.
Preventive programs have been offered for the most differing carcinomas since the middle of the 50ies. Regarding the cervical carcinoma they are based mainly on the morphological and cytological examination of cytosmears of the cervix uteri, what is called the Pap test, which is made on the basis of gynecological routine examinations at regular intervals in women from the 20th year on. By means of the morphology of the cells, the smears are divided into various intensity degrees of dysplastic cellular changes. According to Pap I-V, these intensity degrees are referred to as normal, mild dysplasia, fairly serious dysplasia, serious dysplasia and invasive carcinoma, respectively. If the Pap test leads to a striking result, a small biopsy will be taken and subjected to a histopathologic examination, by which the kind and intensity of the dysplasia are determined and classified as cervical intraepithelial neoplasia (CINI-III).
In spite of all preventive programs, the cervical carcinoma which leads to 400,000 new cases per year is the: most frequent carcinoma in women. This is inter alia due to the fact that up to 30% of the Pap test results are false-negative.
Therefore, it is the object of the present invention to provide a method by which cervical carcinomas can be diagnosed early and reliably. In addition, a differentiation should be possible by this method with respect to benign inflammatory or metaplastic changes of dysplastic preneoplasias.
According to the invention, this is achieved by the subject matters defined in the claims.
The present invention is based on the applicant""s insights that cell cycle regulatory proteins are overexpressed in many carcinomas, e.g., carcinomas of the upper respiratory tract or anogenital carcinomas, particularly cervical carcinoma, and preliminary stages of these carcinomas. Examples of the cell cycle regulatory proteins are cyclins. Cyclin-dependent kinases which regulate the cyclins are to be mentioned particularly. Cyclin-dependent kinase inhibitors which, in turn, regulate the cyclin-dependent kinases, are to be mentioned even more particularly. Examples of the cyclin-dependent kinase inhibitors are the proteins p14, p15, p16, p19, p21 and p27. The applicant has found that the intensity of cell cycle regulatory protein overexpression correlates with the degree of cell dysplasia.